P16050 (LOX15_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Arachidonate 15-lipoxygenase
Short name=15-LOX
EC=1.13.11.33

Alternative name(s):
Arachidonate omega-6 lipoxygenase

Gene names

Name:	ALOX15
Synonyms:	LOG15

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	662 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Converts arachidonic acid to 15S-hydroperoxyeicosatetraenoic acid. Also acts on C-12 of arachidonate as well as on linoleic acid.
Catalytic activity	Arachidonate + O2 = (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate.
Cofactor	Binds 1 iron ion per subunit By similarity.
Pathway	Lipid metabolism; leukotriene D4 biosynthesis.
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the lipoxygenase family. Contains 1 lipoxygenase domain. Contains 1 PLAT domain.

Ontologies

Keywords
Biological process	Leukotriene biosynthesis
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	Iron Metal-binding
Molecular function	Dioxygenase Oxidoreductase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	bone mineralization Inferred from electronic annotation. Source: Compara inflammatory response Traceable author statement PubMed 10200270. Source: ProtInc leukotriene biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW lipid metabolic process Non-traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA
Molecular_function	arachidonate 15-lipoxygenase activity Inferred from electronic annotation. Source: EC iron ion binding Inferred from electronic annotation. Source: InterPro lipoxygenase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.7 Ref.8
	Chain	2 – 662	661	Arachidonate 15-lipoxygenase		PRO_0000220697
Regions
	Domain	2 – 114	113	PLAT
	Domain	115 – 662	548	Lipoxygenase
Sites
	Metal binding	360	1	Iron; catalytic By similarity
	Metal binding	365	1	Iron; catalytic By similarity
	Metal binding	540	1	Iron; catalytic By similarity
	Metal binding	662	1	Iron; via carboxylate; catalytic By similarity
Natural variations
	Natural variant	90	1	D → H. Ref.4 Corresponds to variant rs11568142 [ dbSNP | Ensembl ].		VAR_018746
	Natural variant	102	1	G → V. Corresponds to variant rs41439950 [ dbSNP | Ensembl ].		VAR_035036
	Natural variant	103	1	N → K. Ref.4 Corresponds to variant rs11568099 [ dbSNP | Ensembl ].		VAR_018747
	Natural variant	205	1	R → Q. Ref.4 Corresponds to variant rs11568101 [ dbSNP | Ensembl ].		VAR_018748
	Natural variant	239	1	V → M. Corresponds to variant rs3892408 [ dbSNP | Ensembl ].		VAR_035037
	Natural variant	461	1	A → P. Ref.5 Corresponds to variant rs17852628 [ dbSNP | Ensembl ].		VAR_035038
	Natural variant	560	1	T → M. Corresponds to variant rs34210653 [ dbSNP | Ensembl ].		VAR_035039
Experimental info
	Mutagenesis	418	1	M → V: Catalyzes 15- and 12-lipoxygenation. Ref.9
	Sequence conflict	46	1	E → V in AAC52118. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	P16050 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 9ACF7FE7863A045C	FASTA	662	74,804
	10 20 30 40 50 60 MGLYRIRVST GASLYAGSNN QVQLWLVGQH GEAALGKRLW PARGKETELK VEVPEYLGPL 70 80 90 100 110 120 LFVKLRKRHL LKDDAWFCNW ISVQGPGAGD EVRFPCYRWV EGNGVLSLPE GTGRTVGEDP 130 140 150 160 170 180 QGLFQKHREE ELEERRKLYR WGNWKDGLIL NMAGAKLYDL PVDERFLEDK RVDFEVSLAK 190 200 210 220 230 240 GLADLAIKDS LNVLTCWKDL DDFNRIFWCG QSKLAERVRD SWKEDALFGY QFLNGANPVV 250 260 270 280 290 300 LRRSAHLPAR LVFPPGMEEL QAQLEKELEG GTLFEADFSL LDGIKANVIL CSQQHLAAPL 310 320 330 340 350 360 VMLKLQPDGK LLPMVIQLQL PRTGSPPPPL FLPTDPPMAW LLAKCWVRSS DFQLHELQSH 370 380 390 400 410 420 LLRGHLMAEV IVVATMRCLP SIHPIFKLII PHLRYTLEIN VRARTGLVSD MGIFDQIMST 430 440 450 460 470 480 GGGGHVQLLK QAGAFLTYSS FCPPDDLADR GLLGVKSSFY AQDALRLWEI IYRYVEGIVS 490 500 510 520 530 540 LHYKTDVAVK DDPELQTWCR EITEIGLQGA QDRGFPVSLQ ARDQVCHFVT MCIFTCTGQH 550 560 570 580 590 600 ASVHLGQLDW YSWVPNAPCT MRLPPPTTKD ATLETVMATL PNFHQASLQM SITWQLGRRQ 610 620 630 640 650 660 PVMVAVGQHE EEYFSGPEPK AVLKKFREEL AALDKEIEIR NAKLDMPYEY LRPSVVENSV AI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and primary structure of human 15-lipoxygenase." Sigal E., Craik C.S., Highland E., Grunberger D., Costello L.L., Dixon R.A.F., Nadel J.A. Biochem. Biophys. Res. Commun. 157:457-464(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Characterization and sequence of an additional 15-lipoxygenase transcript and of the human gene." Kritzik M.R., Ziober A.F., Dicharry S., Conrad D.J., Sigal E. Biochim. Biophys. Acta 1352:267-281(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Tongue.
[4]	SeattleSNPs variation discovery resource Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-90; LYS-103 AND GLN-205.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT PRO-461. Tissue: Brain and Lung.
[6]	"Human 15-lipoxygenase gene promoter: analysis and identification of DNA binding sites for IL-13-induced regulatory factors in monocytes." Kelavkar U., Wang S., Montero A., Murtagh J., Shah K., Badr K. Mol. Biol. Rep. 25:173-182(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-46.
[7]	"Arachidonate 15-lipoxygenase (omega-6 lipoxygenase) from human leukocytes. Purification and structural homology to other mammalian lipoxygenases." Sigal E., Grunberger D., Craik C.S., Caughey G.H., Nadel J.A. J. Biol. Chem. 263:5328-5332(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-16.
[8]	"Purification of two forms of arachidonate 15-lipoxygenase from human leukocytes." Izumi T., Raadmark O., Joernvall H., Samuelsson B. Eur. J. Biochem. 202:1231-1238(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-31; 38-45; 157-168 AND 626-631. Tissue: Eosinophil and Leukocyte.
[9]	"A primary determinant for lipoxygenase positional specificity." Sloane D.L., Leung R., Craik C.S., Sigal E. Nature 354:149-152(1991) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF MET-418.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M23892 mRNA. Translation: AAA36182.1.
U88317 Genomic DNA. Translation: AAB49305.1.
AK290309 mRNA. Translation: BAF82998.1.
AY505111 Genomic DNA. Translation: AAR84235.1.
BC029032 mRNA. Translation: AAH29032.1.
U63384 Genomic DNA. Translation: AAC52118.1.

IPI

IPI01016011.

PIR

A31349.

RefSeq

NP_001131.3. NM_001140.3.

UniGene

Hs.73809.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ABT	model	-	A	2-662	[»]

ProteinModelPortal

P16050.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000293761.

PTM databases

PhosphoSite

P16050.

Polymorphism databases

DMDM

126396.

Proteomic databases

PaxDb

P16050.

PRIDE

P16050.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000293761; ENSP00000293761; ENSG00000161905.
ENST00000570836; ENSP00000458832; ENSG00000161905.

GeneID

246.

KEGG

hsa:246.

UCSC

uc002fyh.3. human.

Organism-specific databases

CTD

246.

GeneCards

GC17M004534.

HGNC

HGNC:433. ALOX15.

HPA

CAB004962.
CAB004963.
HPA013859.

MIM

152392. gene.

neXtProt

NX_P16050.

PharmGKB

PA48.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG133298.

HOVERGEN

HBG005150.

InParanoid

P16050.

KO

K00460.

OrthoDB

EOG4W0XCM.

PhylomeDB

P16050.

Enzyme and pathway databases

Pathway_Interaction_DB

il4_2pathway. IL4-mediated signaling events.

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00880.

Gene expression databases

ArrayExpress

P16050.

Bgee

P16050.

CleanEx

HS_ALOX15.

Genevestigator

P16050.

GermOnline

ENSG00000161905. Homo sapiens.

Family and domain databases

Gene3D

2.60.60.20. 1 hit.

InterPro

IPR008976. Lipase_LipOase.
IPR000907. LipOase.
IPR013819. LipOase_C.
IPR020834. LipOase_CS.
IPR020833. LipOase_Fe_BS.
IPR001024. LipOase_LH2.
IPR001885. LipOase_mml.
[Graphical view]

PANTHER

PTHR11771. PTHR11771. 1 hit.

Pfam

PF00305. Lipoxygenase. 2 hits.
PF01477. PLAT. 1 hit.
[Graphical view]

PRINTS

PR00087. LIPOXYGENASE.
PR00467. MAMLPOXGNASE.

SMART

SM00308. LH2. 1 hit.
[Graphical view]

SUPFAM

SSF49723. Lipase_LipOase. 1 hit.
SSF48484. Lipoxygenase. 1 hit.

PROSITE

PS00711. LIPOXYGENASE_1. 1 hit.
PS00081. LIPOXYGENASE_2. 1 hit.
PS51393. LIPOXYGENASE_3. 1 hit.
PS50095. PLAT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P16050.

ChEMBL

CHEMBL2903.

DrugBank

DB01188. Ciclopirox.
DB00179. Masoprocol.
DB00744. Zileuton.

GenomeRNAi

246.

NextBio

979.

SOURCE

Search...

Entry information

Entry name

LOX15_HUMAN

Accession

Primary (citable) accession number: P16050
Secondary accession number(s): A8K2P4, Q8N6R7, Q99657

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 142 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.